Delavirdine pharmacokinetics

The pharmacokinetics of delavirdine 600 mg twice daily did not differ between 16 HIV-negative subjects taking methadone and 15 healthy eontrol subjects. In another study methadone did not affect delavirdine pharmacokinetics. However, delavirdine decreased methadone clearance and increased its AUC by 19%. ... 

Tran JQ, Gerber JG, Kerr BM. Delavirdine clinical pharmacokinetics and drug interactions. Clin Pharmacokinet 2001 40 207-226. 

Wintergerst U, Engelhorn C, Kurowski M, Hoffmann F, Notheis G, Belohradsky BH. Pharmacokinetic interaction of amprenavir in combination with efavirenz or delavirdine in HIV-infected children. AIDS 2000 I4(I2) I866-8. 

By inhibiting their metabolism, ritonavir potentiates the actions of other protease inhibitors. The addition of delavirdine instead of another NNRTI in three patients taking protease inhibitors plus ritonavir further increased the exposure to the protease inhibitors (6). Combining delavirdine with indinavir removes the food restrictions during indinavir administration (4). The superior virological response observed in antiretroviral regimens containing delavirdine and protease inhibitors has been attributed in part to the pharmacokinetic interaction. 

Morse GD, Fischl MA, Shelton MJ, Cox SR, Driver M, DeRemer M, Freimuth WW. Single-dose pharmacokinetics of delavirdine mesylate and didanosine in patients with human immunodeficiency virus infection. Antimicrob Agents Chemother 1997 41(l) 169-74. 

Delavirdine mesylate Route Pregnancy Pharmacokinetic Rapidly... 

Justesen, U. S., Klitgaard, N. A., Brosen, K., and Pedersen, C. (2003) Pharmacokinetic interaction between amprenavir and delavirdine after multiple-dose administration in healthy volunteers. Br. J. Clin. Pharmacol. 55, 100-106. 

Delaviradine is rapidly absorbed by oral administration and peak plasma concentration was obtained in 1 hour. Administration of delaviridine at 400 mg three times daily resulted in peak plasma concentration of 45 mM. The single dose bioavailability of delaviridine tablets relative to oral solution was approximate 85%. The 50% inhibitory concentration for delavirdine against RT activity was 6.0 nM. Delaviridine is extensively bound to plasma protein (-98%). It is metabolized to its N-desisopropyl metabolite in liver, and the pharmacokinetics is nonlinear. Clarithromycin, rifabutin, or ergot alkaloid derivatives are predicted to increase plasma concentration of delaviridine. Skin rashes are the major side effect of delavirdine therapy. Cross-resistance between delavidine and Pis, such as indinavir, nelfinavir, ritonavir, and saquinavir, is unlikely because of action on different enzyme targets. 

Preliminaiy evidence suggests that buprenorphine does not affect the antiretrovirai efficacy or pharmacokinetics of delavirdine and efavirenz. Deiavirdine may increase buprenorphine plasma levels and efavirenz may decrease buprenorphine levels, but the clinical significance has not been fully investigated. Delavirdine given with buprenorphine/naloxone has been shown to slightly prolong the QT interval. 

Delavirdine mesilate 300 mg three times daily was given to 13 HIV-positive subjects for 30 days. Fluconazole 400 mg daily was given to 8 of them on days 16 to 30. No differences in the pharmacokinetics of either drug were noted between the two groups. On the basis of these results, it would appear that no dosage adjustments are needed if these drugs are used together. 

The manufacturer notes that the minimum level of delavirdine was 50% higher than population pharmacokinetic data in 26 patients taking ketoconazole. ... 

Cox SR, Della-Coletta AA, Turner SW, Freimuth WW. Single-dose pharmacokinetic (PK) studies with delavirdine (DLV) mesylate dose proportionality and effects offood and antacid. Intersci ConfAntimicrob Agents Chemolher ( 994) 34, 82. 

Delavirdine may increase the levels of clarithromycin, whereas efavirenz and nevirapine may reduce clarithromycin levels, and increase those of its hydroxy metabolite. Clarithromycin does not appear to affect the pharmacokinetics of delavirdine, efavirenz or nevirapine to a clinically relevant extent. There is no pharmacokinetic interaction between azithromycin and efavirenz. A case of a neuropsychiatric reaction has been attributed to the use of clarithromycin in a man taking nevirapine. 

In 7 HIV-positive patients clarithromycin 500 mg twice daily for 15 days did not cause a clinically significant change in the pharmacokinetics of delavirdine 300 mg three times daily, when compared with 4 other HIV-pos-itive patients taking only delavirdine. The combination was well tolerated and no serious adverse events occurred. However, although delavirdine levels are unaffected, the manufacturer notes that the AUC of clarithromycin was doubled by delavirdine. ... 

It appears that clarithromycin has minimal effects on the pharmacokinetics of the NNRTIs. However, delavirdine may increase levels of clarithromycin. The manufacturer of delavirdine recommends that when the drugs are used concurrently the dose of clarithromycin should be reduced in pa-... 

Cox SR, Borin MT, Driver MR, Levy B, Freimuth WW. Effect of clarithromycin on the steady-state pharmacokinetics of delavirdine in HIV-1 patients. American Society for Microbiology, 2 National Conference on Human Retroviruses, 1995. Abstract 487. 

Delavirdine absorption is reduced by the buffered preparation of didanosine. This interaction would not be expected with the enteric-coated preparation of didanosine. Delavirdine does not affect the pharmacokinetics of zidovudine. There is no pharmacokinetic interaction between efavirenz and zidovudine or lamivudine. There is no ciinicaiiy reievant pharmacokinetic interaction between nevirapine and didanosine, iamivudine, stavudine, zaicit-abine or zidovudine. 

A study in 34 TUV-positive patients taking zidovudine 200 mg three times daily found that delavirdine mesilate 400 mg to 1.2 g daily for 9 days had no clinically significant effect on the pharmacokinetics of zidovudine. ... 

Tran JQ, Petersen C, Garrett M, Hee B, Kerr BM. Pharmacokinetic interaction between amprenavir and delavirdine evidence of induced clearance by amprenavir. Clin... 

Cox SR, Ferry JJ, Batts DH, Carlson GF, Schneck DW, Herman BD, Della-Coletta AA, Chambers JH, Carel BJ, Stewart F, Buss N, Brown A. Delavirdine (D) and marketed protease inhibitors (Pis) pharmacokinetic (PK) interaction studies in healthy volunteers. 4th Conference on Retroviruses and Opportunistic Infections, Washington, 1997. Abstract 372. 

Ferry JJ, Herman BD, Carel BJ, Carlson GF, Batts DH. Pharmacokinetic drug-drug interaction study of delavirdine and indinavir in healthy volunteers. JAcquir launime... 

Cox SR, Schneck DW, Herman BD, Carel BJ, Gulloth BR, Kerr BM, Freimuth WW. Delavirdine (DLV) and nelfinavir (NFV) A pharmacokinetic (PK) drug-drug interaction study in healthy adult volunteers. 5th Conference on Retroviruses and Opportunistic Infections, Chicago, 1998. Abstract 345. 

Shelton MJ, Hewitt RG, Adams J, Della-Coletta A, Cox S, Morse GD. Pharmacokinetics of ritonavir and delavirdine in human immunodeficiency virus-infected patients. Antimicrob Agents Cbemotber (2003) 47, 1694-9. 

Justesen US, Klitgaard NA, Brosen K, Pedersen C. Pharmacokinetic interaction between am-prenavir and delavirdine after multiple-dose administtation in healthy volunteers. BrJ Clin Pharmacol (200 S) 55, 100-6. 

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